Involvement of cyclooxygenase-dependent pathway in contraction of isolated ileum by urotensin II

We previously reported that urotensin II induced biphasic (brief- and long-lasting) contractions and the brief contraction was mediated by acetylcholine release from ganglionic cholinergic neurons in a segment of guinea-pig ileum. In the present work, we studied the mechanism contributing to long-lasting contractions induced by urotensin II. Treatment with 0.1 μM tetrodotoxin, 300 nM ω-conotoxin GVIA (an inhibitor of N-type Ca2+ channels) and 10 μM indomethacin (an inhibitor of cyclooxygenases) markedly inhibited 100 nM urotensin II-induced long-lasting contractions. The addition of 1 μM prostaglandin F2α (PGF2α) caused a limited brief contraction following long-lasting contraction, while 1 μM PGE2 induced marked biphasic contractions. Treatment with neurotoxins inhibited the long-lasting contractions induced by PGF2α and PGE2 without changing the PGE2-induced brief contractions. Treatment with 1 μM atropine markedly inhibited the urotensin II- and PGF2α-induced long-lasting contractions, but was less effective on the PGE2 responses. Treatment with a phospholipase A2 inhibitor decreased the urotensin II-induced contractions. These findings suggest that urotensin II induces, at least partially, long-lasting contractions via PG-sensitive cholinergic neurons and muscarinic acetylcholine receptors in the ileum.